Synthesis of FSH is critical for normal reproductive function in mammals, including humans. Although there is considerable evidence that peptide and sex steroid hormones such as activin and androgens regulate transcription of the FSHBeta gene, the molecular mechanisms of this regulation remain to be elucidated. Since it is not clear how activin and androgens influence the transcription of the FSHBeta gene, I will investigate the role of Smad proteins and the androgen receptor (AR) in the regulation of the mouse FSHBeta gene in a mouse gonadotrope cell line and in vivo using transgenic mice as outlined in the following specific aims. Specific Aim 1" Determine whether Smads and/or AR modulate FSHBeta gene expression in LBT2 cells. Specific Aim 2: Characterize the interactions among Smads, AR, and Pbx/Prep homeodomain Proteins. Specific Aim 3: Determine whether Smads and/or AR regulate FSH Beta gene expression in mouse pituitary gonadotropes in vivo.